A Study of Soticlestat in Adults and Children With Rare Epilepsies

An Adverse Event (AE) was defined any untoward medical occurrence in a subject or clinical study subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign vital sign, symptom, or disease temporally associated with the use of a medicinal product, whether considered related to this medicinal product. A TEAE is defined as any AE that starts or increases in severity during or after the first dose of study drug.

VABS,3rd edition,Parent Caregiver Form:parent-report questionnaire of adaptive functioning/how is individual's routine behaviour at home & in community.4 domains(Communication,Daily Living,Social Skills&Relationships,Problem Behaviors) contained 12 subdomains including items(each scored 0-2).Subdomain scores=sum of item scores within that subdomain.Ranges of subdomain scores are:Communication:Listening&Understanding(0-78);Talking(0-98);Reading&Writing(0-76),Daily Living:Caring for Self(0-110);Caring for Home(0-60);Living in Community(0-116),Social Skills&Relationships:Relating to Others(0-86);Playing&Using Leisure Time(0-72);Adapting(0-66),Problem Behaviors:Section A(0-26);Section B(0-22),Section C(0-40).For 1st 3 domains,higher subdomain scores=higher adaptive functioning,positive CFB=improvement.For Problem Behaviors,higher subdomain scores=more problem behaviors,negative CFB=improvement(reduction in problem behaviors).No subdomain scores combined to compute any total score.

The ABC-C measures psychiatric symptoms and behavioral disturbance exhibited by individuals across 5 subscales with 58 items: Irritability subscale (15 items); Lethargy/Social Withdrawal subscale (16 items); Stereotypic Behavior subscale (7 items); Hyperactivity subscale (16 items); and Inappropriate Speech subscale (4 items). Each item is rated on a scale of 0 to 3 ("not at all a problem" to "the problem is severe in degree"). The total score was calculated by summing the scores on all 58 items where the total scores ranged from 0 to 174. Higher scores indicate more severity in psychiatric symptoms and behavioral disturbance. Negative change from baseline scores represents improvement. Positive change from baseline scores represents worsening.

The ABC-C measures psychiatric symptoms and behavioral disturbance exhibited by individuals across 5 subscales with 58 items: Irritability subscale (15 items: Ranges from 0 to 45); Lethargy/Social Withdrawal subscale (16 items: Ranges from 0 to 48); Stereotypic Behavior subscale (7 items: Ranges from 0 to 21); Hyperactivity subscale (16 items: Ranges from 0 to 48); and Inappropriate Speech subscale (4 items: Ranges from 0 to 12). Each item is rated on a scale of 0 to 3 ("not at all a problem" to "the problem is severe in degree"). Subscale scores are calculated as the sum of items within the subscale. Higher subscale scores indicate more severity in psychiatric symptoms and behavioral disturbance. Negative change from baseline score represents improvement. Positive change from baseline score represents worsening.

Suicidal ideation and behavior was assessed in participants with at least 6 years of age using the C-SSRS. The C-SSRS is a 3-part scale that measures suicidal ideation (eg, participants endorses thoughts about a wish to be dead or has other thoughts of suicide), intensity of ideation (frequency), and suicidal behavior (actually, interrupted, and aborted attempts at suicide). SI=Suicidal Ideation; SB=Suicidal Behavior and NSSJB=Non-suicidal Self-injurious Behavior for the categories reported. BL denotes Baseline, V denotes Visit and W denotes Week in the categories.

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

BL denotes Baseline, CFB denotes Change from Baseline, W denotes Week, HDL denotes High Density Lipid and LDL denotes Low Density Lipid for the reported categories.

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

The percentage of the specified blood cells relative to total leukocyte count was determined and reported. BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.

BL denotes BL, CFB denotes Change from baseline and W denotes Week for the reported categories.

ALT: Alanine Aminotransferase, AST: Aspartate Aminotransferase, HGB: Hemoglobin, ULN: Upper limit of normal, LLN: Lower limit of normal and UREAN: Urea Nitrogen for the specified categories. mmol/L indicates millimoles per liter. Data is reported only for participants who had potentially clinically significant values.

Data is reported only for participants who had potentially clinically significant values.

The criteria for defining clinical significance for weight category was the participants less than equal to (<=)10 years of age with weight below minus (-)2standard deviation (SD) of the median weight of the same age and gender per world health organization (WHO) growth chart and for height category was the participants less than (<)18 years of age with height below -2SD of the median weight of the same age and gender per WHO growth chart.

Change from Baseline is denoted as CFB.

Change from Baseline is denoted as CFB.

Change from Baseline is denoted as CFB.

CGI-S is used to obtain an assessment of symptom severity, focusing on clinicians' observations of the subject's current cognitive, functional, and behavioral performance. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (among the most severely ill participants). BL denotes BL, CFB denotes Change from baseline and W denotes Week for the reported categories.